This invention relates to the preparation of propamocarb from dimethylaminopropylamine and dipropyl carbonate using an enzyme catalyst. Propyl 3-(dimethylamino)propylcarbamate or Propamocarb (CAS Registry Number: 24579-73-5) is a systemic fungicide used in agriculture and horticulture on a wide variety of plants species (Papvizas et al., 1978, Phytopathology vol. 68 p. 1667-71).
The hydrochloride salt of Propamocarb is marketed under the trademark Previcur™ by Bayer CropScience. Propamocarb can be further derivatized to form the broad-spectrum fungicide dimethyl-[3-(propoxycarbonylamino)propyl]ammonium O-ethylphosphonate (See U.S. Pat. No. 6,339,103). Propamocarb can be further derivatized to form the broad-spectrum fungicides dimethyl[3-(propoxycarbonylamino)propyl]ammonium phosphate and dimethyl-[3-(propoxycarbonylamino)propyl]ammonium phosphite.
The existing synthetic route combines 3-dimethylaminopropylamine (DMAPA) and propyl chloroformate to produce Propamocarb (See p. 94, Pesticide Synthesis Handbook, Thomas A Unger, 1996). The reaction can be performed in an inert organic solvent such as toluene or in water, though higher product yields have been demonstrated using propanol as a solvent (See EP 1 254 894 A1).
Chloroformates are produced by the reaction of phosgene with alcohols or phenols. Hydrogen chloride is evolved during the reaction and is collected in a tower with recovered excess phosgene (See Kreutzberger, C. B. 2003. Chloroformates and Carbonates. Kirk-Othmer Encyclopedia of Chemical Technology). Chloroformates are highly toxic when inhaled. The AEGL-3 value for propyl chloroformate for a 10-minute exposure is 20 ppm in air, meaning exposures at or above that level could lead to life-threatening health effects. There is thus a need for a route to Propamocarb and its derivatives that avoids toxic intermediates such as chloroformates.